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Exploiting the curative potential of adoptive T‐cell therapy for cancer
Open accessAbstract
Summary: Adoptive T‐cell therapy (ACT) is a potent and flexible cancer treatment modality that can induce complete, durable regression of certain human malignancies. Long‐term follow‐up of patients receiving tumor‐infiltrating lymphocytes (TIL s) for metastatic melanoma reveals a substantial subset that experienced complete, lasting tumor regression – and may be cured. Increasing evidence points to mutated gene products as the primary immunological targets of TIL s from melanomas. Recent technological advances permit rapid identification of the neoepitopes resulting from these somatic gene mutations and of T cells with reactivity against these targets. Isolation and adoptive transfer of these T cells may improve TIL therapy for melanoma and permit its broader application to non‐melanoma tumors. Extension of ACT to other malignancies may also be possible through antigen receptor gene engineering. Tumor regression has been observed following transfer of T cells engineered to express chimeric antigen receptors against CD 19 in B‐cell malignancies or a T‐cell receptor against NY‐ESO‐1 in synovial cell sarcoma and melanoma. Herein, we review recent clinical trials of TIL s and antigen receptor gene therapy for advanced cancers. We discuss lessons from this experience and consider how they might be applied to realize the full curative potential of ACT.
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“Currently, another hot spot in cancer gene therapy is the modifications of the host cells to enhance anticancer immune responses, 68 or to increase resistance to chemo-and radiotoxicity. 3”
From CRISPR-Cas9: a new and promising player in gene therapy (2015) · cites this paper as [68]
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Metadata
- Authors
- Hinrichs, C. S., & Rosenberg, S. A.
- Affiliations
- National Cancer Institute (US)
- Corresponding author
- Hinrichs, Christian S.
- Venue
- Immunological Reviews
- Publisher
- Wiley
- Published
- 2013-12-13
- Volume
- 257
- Issue
- 1
- Pages
- 56-71
- ISSN
- 0105-2896 (ISSN-L)
- 1600-065X
- PMC
- PMC3920180
- OpenAlex
- W2150145041
- Cited by
- 466
- References
- 137
- Citations by year
- 2026: 6 · 2025: 20 · 2024: 16 · 2023: 25 · 2022: 36 · 2021: 32 · 2020: 38 · 2019: 39 · 2018: 55 · 2017: 59 · 2016: 56 · 2015: 56 · 2014: 26 · 2013: 1
- FWCI
- 4.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Immunological Reviews (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (ZIABC011478)
- Topics
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- adoptive T cell therapy, tumor-infiltrating lymphocytes, metastatic melanoma, tumor regression, neoantigens, somatic mutations, chimeric antigen receptor, NY-ESO-1, CD19, B-cell malignancies, synovial sarcoma, cancer immunotherapy
- MeSH terms
- Animals, Antigens, Neoplasm, Humans, Neoplasms, Receptors, Antigen, T-Cell, Protein Engineering, Immunotherapy, Adoptive, Lymphocytes, Tumor-Infiltrating
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